1. CYP24A1 affected macrophage polarization through degradation of vitamin D as a candidate biomarker for ovarian cancer prognosis.
- Author
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Lin Y, Chen J, Xin S, Lin Y, Chen Y, Zhou X, Chen H, and Li X
- Subjects
- Female, Humans, Prognosis, Animals, Cell Line, Tumor, Mice, Gene Expression Regulation, Neoplastic, Macrophage Activation, Vitamin D3 24-Hydroxylase metabolism, Vitamin D3 24-Hydroxylase genetics, Ovarian Neoplasms immunology, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Macrophages immunology, Macrophages metabolism, Vitamin D metabolism, Vitamin D pharmacology, Biomarkers, Tumor metabolism, Biomarkers, Tumor genetics
- Abstract
Ovarian cancer (OC) is a fatal gynecological malignancy with a poor prognosis in which mitochondria-related genes are involved deeply. In this study, we aim to screen mitochondria-related genes that play a role in OC prognosis and investigate its effects. Through single-cell sequencing technology and bioinformatics analysis, including TCGA ovarian cancer data analysis, gene expression signature analysis (GES), immune infiltration analysis, Gene Ontology (GO) enrichment analysis, Gene Set Enrichment Analysis (GSEA), and Principal Component Analysis (PCA), our findings revealed that CYP24A1 regulated macrophage polarization through vitamin D (VD) degradation and served as a target gene for the second malignant subtype of OC through bioinformatics analyses. For further validation, the expression and function of CYP24A1 in OC cells was investigated. And the expression of CYP24A1 was much higher in carcinoma than in paracancerous tissue, whereas the VD content decreased in the OC cell lines with CYP24A1 overexpression. Moreover, macrophages were polarized towards M1 after the intervention of VD-treated OC cell lines and inhibited the malignant phenotypes of OC. However, the effect could be reversed by overexpressing CYP24A1, resulting in the polarization of M2 macrophages, thereby promoting tumor progression, as verified by constructing xenograft models in vitro. In conclusion, our findings suggested that CYP24A1 induced M2 macrophage polarization through interaction with VD, thus promoting the malignant progression of OC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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